KEYMAKER-U04 Substudy 04D: A Clinical Study of New Treatments Given With Enfortumab Vedotin and Pembrolizumab in People With Urothelial Cancer (MK-3475-04D/KEYMAKER-U04)

Phase 2RecruitingNCT07232602

Merck Sharp & Dohme LLC55 enrolled

Overview

Researchers are looking for new ways to treat people with urothelial cancer (UC) that is locally advanced or metastatic. The standard treatment for locally advanced or metastatic UC is enfortumab vedotin (EV) given with pembrolizumab. The goals of this study are to learn about: * The safety of the study treatment when given with standard treatment and if people tolerate it * The number of people who have the cancer respond (cancer gets smaller or goes away) with the new study treatment when given with standard treatment.

This is a substudy of the master protocol MK-3475-U04 (KEYMAKER-U04)

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Bladder Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has histologically documented urothelial carcinoma (UC) that is locally advanced and unresectable or metastatic * Must provide a newly obtained or archival tumor tissue sample (core or excisional biopsy) * Must not have received prior systemic therapy for locally advanced or metastatic UC * If infected with Human Immunodeficiency Virus (HIV), has well controlled HIV on antiretroviral therapy * If positive for hepatitis B surface antigen, has received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and has undetectable HBV viral load before randomization * If participant has a history of hepatitis C virus (HCV), has undetectable HCV viral load before randomization Exclusion Criteria: The main exclusion criteria include but are not limited to the following: * Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing * Has active keratitis or corneal ulcerations * Has active inflammatory bowel disease requiring immunosuppressive medication, or previous history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea) * Has uncontrolled, significant cardiovascular disease or cerebrovascular disease within the 6 months preceding study intervention * Has a history of uncontrolled diabetes * Has pleural effusion, ascites, and/or pericardial effusion that are symptomatic or require repeated drainage * Has active autoimmune disease that has required systemic treatment in the past 2 years * Has known additional malignancy that is progressing or has required active treatment within the past 2 years * Has known active central nervous system metastases and/or carcinomatous meningitis * Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids, or has current pneumonitis/interstitial lung disease * Has an active infection requiring systemic therapy * If infected with HIV, has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease * Has concurrent active HBV and HCV infection * Has a history of stem cell/solid organ transplant

Locations (16)

UCSF Medical Center at Mission Bay ( Site 5044)

San Francisco, California, United States

RECRUITING

University of Chicago Medical Center ( Site 5037)

Chicago, Illinois, United States

RECRUITING

Cleveland Clinic Taussig Cancer ( Site 5036)

Cleveland, Ohio, United States

RECRUITING

Huntsman Cancer Institute ( Site 5041)

Salt Lake City, Utah, United States

RECRUITING

FALP ( Site 5151)

Santiago, Region M. de Santiago, Chile

RECRUITING

CHU de Bordeaux Hop St ANDRE ( Site 5607)

Bordeaux, Gironde, France

RECRUITING

Rambam Health Care Campus ( Site 5501)

Haifa, Israel

RECRUITING

Rabin Medical Center ( Site 5504)

Petah Tikva, Israel

RECRUITING

Nederlands Kanker Instituut Antoni van Leeuwenhoek (NKI AVL) ( Site 5302)

Amsterdam, North Holland, Netherlands

RECRUITING

Erasmus MC ( Site 5303)

Rotterdam, South Holland, Netherlands

RECRUITING

...and 6 more locations

Outcomes

Primary Outcomes

Number of Participants Who Experience an Adverse Event (AE)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants that experience AEs will be reported.

Time frame: Up to approximately 27 months

Number of Participants Who Experience a Dose Limiting Toxicity (DLT)

DLT will be defined as any drug-related AE observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next treatment. The number of participants who experience a DLT as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 will be presented.

Time frame: Up to approximately 21 days

Number of Participants Who Discontinue Study Treatment Due to an AE

Time frame: Up to approximately 24 months

Objective Response Rate (ORR) as Assessed by Investigator

ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Investigator will be presented.

Time frame: Up to approximately 58 months

Secondary Outcomes

Duration of Response (DOR) as Assessed by Investigator

For participants who demonstrate a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by investigator will be presented.

Time frame: Up to approximately 58 months

Serum Maximum Concentration (Cmax) of MK-3120 Antibody-Drug Conjugate (ADC)

Cmax is defined as the peak concentration over the dosing interval. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax of MK-3120 ADC.